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Specific protein methylation defects and gene expression perturbations in coactivator-associated arginine methyltransferase 1-deficient mice.

Arginine methylation has been implicated in the regulation of gene expression. The coactivator-associated arginine methyltransferase 1 (CARM1/PRMT4) binds the p160 family of steroid receptor coactivators (SRCs). This association enhances transcriptional activation by nuclear receptors. Here, we show that embryos with a targeted disruption of CARM1 are small in size and die perinatally. The methylation of two known CARM1 substrates, poly(A)-binding protein (PABP1) and the transcriptional cofactor p300, was abolished in knockout embryos and cells. However, CARM1-dependent methylation of histone H3 was not observed. Furthermore, estrogen-responsive gene expression was aberrant in Carm1-/- fibroblasts and embryos, thus emphasizing the role of arginine methylation as a transcription activation tag. These findings provide genetic evidence for the essential role of CARM1 in estrogen-mediated transcriptional activation.

Pubmed ID: 12756295


  • Yadav N
  • Lee J
  • Kim J
  • Shen J
  • Hu MC
  • Aldaz CM
  • Bedford MT


Proceedings of the National Academy of Sciences of the United States of America

Publication Data

May 27, 2003

Associated Grants

  • Agency: NCI NIH HHS, Id: CA16672
  • Agency: NIDDK NIH HHS, Id: DK62248-01
  • Agency: NIEHS NIH HHS, Id: ES07784

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cells, Cultured
  • E1A-Associated p300 Protein
  • Gene Expression
  • Genes, Lethal
  • Methylation
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • Nuclear Proteins
  • Poly(A)-Binding Protein I
  • Protein-Arginine N-Methyltransferases
  • Trans-Activators